Methyl 2-(Phenylsulfinyl)acetate

[14090-83-6]  · C9H10O3S  · Methyl 2-(Phenylsulfinyl)acetate  · (MW 198.26)

(synthetic equivalent of a vinyl organometallic species; undergoes addition/elimination to aldehydes to give conjugated dienoates or 4-hydroxy (2E)-enoates)

Physical Data: mp 53-55 °C; bp 130-131 °C/0.5 mmHg.

Form Supplied in: solid; widely available.

Handling, Storage, and Precautions: fp >100 °C.

Knoevenagel Condensation with Aldehydes.

The sodium and lithium enolates of methyl 2-(phenylsulfinyl)acetate are very stable and tend not to react with aldehydes under normal conditions; however, the Knovenagel amine-catalyzed condensation1,2 occurs under mild conditions to give 3-aryl-2-(phenylsulfinyl)(2E)-propenoate methyl esters stereoselectively (eq 1) in a 98:2 (E:Z) ratio as determined by Tf2O/dimethyl sulfide reduction followed by GLC analysis. These compounds are useful because they are powerful dienophiles in a variety of Diels-Alder reactions.

Preparation of 3-Hydroxy Enoates.

Under similar Knovenagel conditions, methyl 2-(phenylsulfinyl)acetate can undergo addition to afford the sulfinyl condensation product; base-catalyzed deconjugation, a [2,3]-sigmatropic shift, and hydrolysis of the sulfenate ester intermediate then affords 4-hydroxy (2E)-enoates3-5 in one pot (eqs 2 and 3).

Preparation of 1,3-Dienoates from Alkenes.

Trost et al.5 have demonstrated that the palladium-catalyzed addition of methyl 2-(phenylsulfinyl)acetate to palladium p-allyl complexes gives intermediate allylsulfinates, which undergo a standard thermal elimination of the sulfoxide group to afford 2,4-dienoates efficiently from alkenes (eqs 4 and 5).

Alkylation Followed by Elimination to Give Enones.

Despite the low reactivity of the enolates, methyl 2-(phenylsulfinyl)acetate can be induced to undergo nucleophilic attack. Methyl cyclobutenecarboxylate6 can be prepared by deprotonation of the reagent with a solution of 2 equiv of Sodium Hydride and 1,3-Diiodopropane in DMF to give the cyclic product; pyrolysis at 160 °C affords the cyclobutene product in a low (39%) overall yield (eq 6).

Benzylic bromides also undergo an efficient one-pot alkylation/elimination using Potassium Carbonate in the presence of a phase-transfer catalyst such as aliquat-336 in DMF to afford trans-unsaturated esters in good yields (eq 7).7

Synthesis of 1,4-Dicarbonyl Compounds via Pummerer Reaction.

Treatment of methyl 2-(phenylsulfinyl)acetate with Tin(II) Trifluoromethanesulfonate effects conversion of the sulfoxide group to the Pummerer intermediate. This reacts with silyl enol ethers in the presence of N-(Trimethylsilyl)imidazole to afford 1,4-dicarbonyl compounds8 containing a phenylthio group, which can be oxidized and thermally eliminated to give unsaturated dicarbonyl compounds or reductively removed to give the saturated analogs (eq 8).

Michael Addition Reactions of Methyl 2-(Phenylsulfinyl)acetate.

The potassium salt of methyl 2-(phenylsulfinyl)acetate can be induced to undergo a Michael addition in the presence of 18-Crown-6. Subsequent thermal elimination of the sulfoxide group in refluxing xylenes affords the a,b-unsaturated enone, via equilibration of the double bond into conjugation with the ketone. This reaction constitutes the synthetic equivalent of an acetate anion addition to an a,b-unsaturated system with retention of unsaturation (eq 9).9

A tandem Michael addition/enolate acylation reaction with a,b-unsaturated methyl ketones is possible in the presence of Magnesium Methoxide, giving rise to a 1,3-diketocyclohexane system; on heating, this eliminates the sulfoxide group to give an aromatic resorcinol system (eq 10).10

1. Tanikaga, R.; Nakayama, K.; Tanaka, K.; Kaji, A. CC 1984, 87.
2. Tanikaga, R.; Konya, N.; Tamura, T.; Kaji, A. JCS(P1) 1987, 825.
3. Tanikaga, R.; Nozaki, Y.; Tamura, K.; Kaji, A. CL 1982, 1703.
4. Tanikaga, R.; Nozaki, Y.; Tamura, T.; Kaji, A. S 1983, 134.
5. Trost, B. M.; Lautens, M. T 1987, 43, 4817.
6. Wilson, S. R.; Phillips, L. R.; Pelister, Y.; Huffman, J. C. JACS 1979, 101, 7373.
7. Chong-ying, X.; Guang-jian, L.; Zhen, Z. SC 1987, 17, 1839.
8. Shimizu, M.; Akiyama, T.; Mukaiyama, T. CL 1984, 1531.
9. Cantrell Jr., W. R.; Davies, H. M. L. JOC 1991, 56, 723.
10. Jaxa-Chamiec, A. A.; Sammes, P. G.; Kennewell, P. D. JCS(P1) 1980, 170.

Dinos Santafianos

Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ, USA

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